CA2320160C - Modulation of hair growth - Google Patents
Modulation of hair growth Download PDFInfo
- Publication number
- CA2320160C CA2320160C CA002320160A CA2320160A CA2320160C CA 2320160 C CA2320160 C CA 2320160C CA 002320160 A CA002320160 A CA 002320160A CA 2320160 A CA2320160 A CA 2320160A CA 2320160 C CA2320160 C CA 2320160C
- Authority
- CA
- Canada
- Prior art keywords
- compound
- androgen
- hair growth
- compound comprises
- skin
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Expired - Fee Related
Links
Classifications
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
- A61Q7/02—Preparations for inhibiting or slowing hair growth
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/045—Hydroxy compounds, e.g. alcohols; Salts thereof, e.g. alcoholates
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/075—Ethers or acetals
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/335—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin
- A61K31/35—Heterocyclic compounds having oxygen as the only ring hetero atom, e.g. fungichromin having six-membered rings with one oxygen as the only ring hetero atom
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/513—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim having oxo groups directly attached to the heterocyclic ring, e.g. cytosine
- A61K31/515—Barbituric acids; Derivatives thereof, e.g. sodium pentobarbital
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
- A61K8/34—Alcohols
- A61K8/347—Phenols
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4913—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid
- A61K8/492—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having five membered rings, e.g. pyrrolidone carboxylic acid having condensed rings, e.g. indol
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4906—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom
- A61K8/4926—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with one nitrogen as the only hetero atom having six membered rings
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/494—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom
- A61K8/4953—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with more than one nitrogen as the only hetero atom containing pyrimidine ring derivatives, e.g. minoxidil
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/49—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds
- A61K8/4973—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom
- A61K8/498—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing heterocyclic compounds with oxygen as the only hetero atom having 6-membered rings or their condensed derivatives, e.g. coumarin
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K8/00—Cosmetics or similar toiletry preparations
- A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
- A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
- A61K8/63—Steroids; Derivatives thereof
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
- A61Q7/00—Preparations for affecting hair growth
Landscapes
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Epidemiology (AREA)
- Birds (AREA)
- Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Dermatology (AREA)
- Emergency Medicine (AREA)
- Cosmetics (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
Abstract
Mammalian hair growth may be modulated by applying to the skin a compound that induces or activates the conjugation of an androgen.
Description
MODULATION OF '~3AIR GROWTH
Hackaround of the _TnventiQn The invention relates to modulating hair growth in mammals.
A main function of mammalian hair is to provide environmental protection. However, that function hae largely been lost in humans, in whom hair is kept or removed from various parts of the body essentially for cosmetic reasons. For example, it is generally preferred to have hair on the scalp but not on the face.
Various procedures have been employed to remove unwanted hair, including shaving, electrolysis, depilatory I5 creams or lotions, waxing, plucking, and therapeutic antiandrogens. These conventional procedures generally have drawbacks associated with them. Shaving, for instance, can cause nicks and cuts, and can leave a perception of an increase in the rate of hair regrowth. Shaving also can leave an undesirable stubble. Electrolysis, on the other hand, can keep a treated area free of hair for prolonged periods of time, but can be expensive, painful, and sometimes leaves scarring. Depilatory creams, though very effective, typically are not recommended for frequent use due to their high irritancy potential. Waxing and plucking can cause pain, discomfort, and poor removal of short hair.
Finally, antiandrogens -- which have been used to treat female hirsutism -- can have unwanted side effects'.
It has previously been disclosed that the rate and character of hair growth can be altered by applying to the skin inhibitors of certain enzymes. These inhibitors include inhibitors of 5-alpha reductase, ornithine decarboxylase, S-adenosylmethionine decarboxylase, gamma-glutamyl transpeptidase, and transglutaminase. See, for example, Hreuer et al., U.S. Pat. No. 4,885,289; Shander, U.S. Pat. No. 4,720,489; Ahluwalia, U.S. Pat. No. 5,095,007;
Ahluwalia et al., U.S. Pat. No. 5,096,911; Shander et al., U.S. Pat. No. 5,132,293; and Shander et al., U.S. Pat. No.
5,143,925.
The growth of hair results from many complex and interactive processes. In one process sex steroid androgens, particularly testosterone, act on, for example, beard hair follicles on the face to stimulate hair growth.
Hut these same androgens can inhibit hair growth on the scalp, particularly in those that have a genetic predisposition for male-pattern baldness or androgenetic alopecia.
Cytochrome P450s, epoxide hydrolases, glutathione-S-transferases, UDP-glucuronosyltransferases (UGTs), and sulfotransferases (STs) are families of enzymes that are involved in the metabolism of xenobiotics and other substances that are endogeneous to the human body.
Generally, the enzymes catalyze the conversion of a substrate (e.g., a particular steroid) to a form that is more readily eliminated from the body. For example, "' glutathione-S-tranferases catalyze the conjugation of the substrate with glutathione; UGTs catalyze the conjugation of substrate with glucuronic acid; and STs catalyze the conjugation of the substrate with a sulfonate moiety. It is believed that these substrate conjugates are more water soluble than the substrate itself, and thus more readily eliminated from the body. Some of these enzymes can be induced by compounds, such as 3-methylcholanthrene and phenobarbital.
Steroids are substrates for several isoforms of UGT, with overlapping specificities. For example, rat liver UGTr-3 catalyzes the glucuronidation of dihydrotestosterone, testosterone and a-estradiol, whereas in addition to these steroids UGTr-2 also catalyzes 4-hydroxybiphenyl, chloramphenicol and 4-methylumbelliferone glucuronoconjugation (Chen et al., Biochem. 32: 10648-x0657).
Summary of the Invention In one aspect, the invention features modulating hair growth by topical application of a compound that induces or activates the conjugation of an androgen (e. g., testosterone) that is involved in hair growth. By "induces"
or "activates", we mean that the compound increases the conjugating enzyme levels in the hair follicle cells and/or increases the catalytic activity of the conjugating enzyme for conjugation. The compound may, for example, induce or activate a UGT or an ST for which the androgen serves as the substrate.
The modulation in hair growth depends on whether the hair growth selected for treatment is androgen-stimulated hair growth (e.g., beard hair and torso hair generally in humans) or hair growth that is not androgen-stimulated (e.g., scalp hair in humans). Topical application of t.~e compound in a dermato3.ogically acceptable vehicle to an area of skin having androgen-stimulated hair growth generally causes a reduction in hair growth. Topical application of the compound in a dermatologically acceptable vehicle to an area of skin having hair growth (i.e., from the scalp) that is reduced in the presence of androgens, (e.g., because of androgenic alopecia) generally causes an increase in hair growth.
In another aspect, the invention features modulating hair growth by topical application of a compound that induces or activates a UGT.
Hackaround of the _TnventiQn The invention relates to modulating hair growth in mammals.
A main function of mammalian hair is to provide environmental protection. However, that function hae largely been lost in humans, in whom hair is kept or removed from various parts of the body essentially for cosmetic reasons. For example, it is generally preferred to have hair on the scalp but not on the face.
Various procedures have been employed to remove unwanted hair, including shaving, electrolysis, depilatory I5 creams or lotions, waxing, plucking, and therapeutic antiandrogens. These conventional procedures generally have drawbacks associated with them. Shaving, for instance, can cause nicks and cuts, and can leave a perception of an increase in the rate of hair regrowth. Shaving also can leave an undesirable stubble. Electrolysis, on the other hand, can keep a treated area free of hair for prolonged periods of time, but can be expensive, painful, and sometimes leaves scarring. Depilatory creams, though very effective, typically are not recommended for frequent use due to their high irritancy potential. Waxing and plucking can cause pain, discomfort, and poor removal of short hair.
Finally, antiandrogens -- which have been used to treat female hirsutism -- can have unwanted side effects'.
It has previously been disclosed that the rate and character of hair growth can be altered by applying to the skin inhibitors of certain enzymes. These inhibitors include inhibitors of 5-alpha reductase, ornithine decarboxylase, S-adenosylmethionine decarboxylase, gamma-glutamyl transpeptidase, and transglutaminase. See, for example, Hreuer et al., U.S. Pat. No. 4,885,289; Shander, U.S. Pat. No. 4,720,489; Ahluwalia, U.S. Pat. No. 5,095,007;
Ahluwalia et al., U.S. Pat. No. 5,096,911; Shander et al., U.S. Pat. No. 5,132,293; and Shander et al., U.S. Pat. No.
5,143,925.
The growth of hair results from many complex and interactive processes. In one process sex steroid androgens, particularly testosterone, act on, for example, beard hair follicles on the face to stimulate hair growth.
Hut these same androgens can inhibit hair growth on the scalp, particularly in those that have a genetic predisposition for male-pattern baldness or androgenetic alopecia.
Cytochrome P450s, epoxide hydrolases, glutathione-S-transferases, UDP-glucuronosyltransferases (UGTs), and sulfotransferases (STs) are families of enzymes that are involved in the metabolism of xenobiotics and other substances that are endogeneous to the human body.
Generally, the enzymes catalyze the conversion of a substrate (e.g., a particular steroid) to a form that is more readily eliminated from the body. For example, "' glutathione-S-tranferases catalyze the conjugation of the substrate with glutathione; UGTs catalyze the conjugation of substrate with glucuronic acid; and STs catalyze the conjugation of the substrate with a sulfonate moiety. It is believed that these substrate conjugates are more water soluble than the substrate itself, and thus more readily eliminated from the body. Some of these enzymes can be induced by compounds, such as 3-methylcholanthrene and phenobarbital.
Steroids are substrates for several isoforms of UGT, with overlapping specificities. For example, rat liver UGTr-3 catalyzes the glucuronidation of dihydrotestosterone, testosterone and a-estradiol, whereas in addition to these steroids UGTr-2 also catalyzes 4-hydroxybiphenyl, chloramphenicol and 4-methylumbelliferone glucuronoconjugation (Chen et al., Biochem. 32: 10648-x0657).
Summary of the Invention In one aspect, the invention features modulating hair growth by topical application of a compound that induces or activates the conjugation of an androgen (e. g., testosterone) that is involved in hair growth. By "induces"
or "activates", we mean that the compound increases the conjugating enzyme levels in the hair follicle cells and/or increases the catalytic activity of the conjugating enzyme for conjugation. The compound may, for example, induce or activate a UGT or an ST for which the androgen serves as the substrate.
The modulation in hair growth depends on whether the hair growth selected for treatment is androgen-stimulated hair growth (e.g., beard hair and torso hair generally in humans) or hair growth that is not androgen-stimulated (e.g., scalp hair in humans). Topical application of t.~e compound in a dermato3.ogically acceptable vehicle to an area of skin having androgen-stimulated hair growth generally causes a reduction in hair growth. Topical application of the compound in a dermatologically acceptable vehicle to an area of skin having hair growth (i.e., from the scalp) that is reduced in the presence of androgens, (e.g., because of androgenic alopecia) generally causes an increase in hair growth.
In another aspect, the invention features modulating hair growth by topical application of a compound that induces or activates a UGT.
In another aspect, the invention features modulating hair growth by topical application of a compound that induces or activates an ST.
In another aspect, the invention features modulating hair growth by topical application of a compound that induces or activates the conversion of an androgen involved in hair growth to a less active (e. g., more water soluble) metabolite.
Other features and advantages of the invention will IO be apparent from the Description of Preferred Embodiments thereof, and from the claims.
Descrio~ion of Preferre Embodim rr,~
Compounds that activate or induce UGTs are known.
Such compounds include ethoxyquin, 5,7-dihydroxy-4'-methoxyflavone, butyihydroxyanisole, Phenobarbital, naringenin, butylhydroxytoluene, flavone, tioconazole, traps-1,2-bis(2-pyridyl)ethylene, 7,4'-isoflavandiol, (equol), galangin, 7-hydroxy-4'-methoxyisoflavone (formononetin), 5,4'-dihydroxy-7-methoxyisoflavone (prunetin), and daidzein. These compounds induce UGTs .~
relevant to testosterone glucononidation.
Examples of androgens that may be conjugated include testosterone, dihydrotestosterone, androstenedione, androstenediols, and dehydroepiandrosterone.
It is believed that the compounds act according to the pathway shown below (in which testosterone is used as an example):
swet~aon< -~. Ert~G~ow~soaW.aa,~
w~G~~c~) c«~uwiv. E~m., ~,~"~,k"",;~" ...... ~'~~t~ ~toaauter~se) T.~~.1 c.ue:.~) Denafed Bbl~nl Aauney --1 - 4 _ HawGwrthSomuVuos(~cilp) The compound may induce or activate, for example, UGTs that catalyze the conjugation of testosterone with glucuronic acid (donated from uridine diphosphoglucuronic acid) or STs that catalyze the conjugation of testosterone with a sulfonate group (donated from 3'-phosphoadenoaine S~-phosphosulfate).
The compound preferably is incorporated in a topical composition that includes a non-toxic dermatologically acceptable vehicle or carrier which is adapted to be spread l0 upon the skin. Examples of, suitable vehicles are acetone, alcohols, or a cream, lotion, or gel which can effectively deliver the active compound. A vehicle is disclosed in U.S.
Patent No. 5,648,394. In addition, a penetration enhancer may be added to the vehicle to further enhance the effectiveness of the formulation.
The concentration of the compound in the composition may be varied over a wide range up to a saturated solution, preferably from 0.1% to 30% by weight or even more; the reduction or increase in hair growth rises as the amount of inhibitor applied increases per unit area of skin. The-maximum amount effectively applied is limited only by the rate at which the compound penetrates the skin. The effective amounts may range, for example, from 10 to 3000 micrograms or more per square centimeter of skin.
A composition may include more than one of the compounds.
The composition should be topically applied to a selected area of the body from which it is desired to reduce hair growth (if the hair growth is androgen-stimulated hair growth) or increase hair growth (if the hair loss is androgen dependent). For example, in humans the composition can be applied to the face, particularly to the beard area of the face, i.e., the cheek, neck, upper lip, and chin to obtain a reduction in hair growth. .The composition can also be applied to the legs, arms, torso or armpits to obtain a reduction in hair growth. The composition can be applied to ~he scalp to obtain an increase in hair growth. The composition is particularly suitable for reducing the growth of unwanted hair in women suffering from hirsutism or other similar conditions.
in humans, the composition, for example, may be applied once or twice a day, or even more frequently, for two weeks to six months (e.g., three months) to achieve a perceived effect. Reduction in hair growth is demonstrated when the frequency of hair removal is reduced or the subject perceives less hair on the treated site, or quantitatively, when the weight of hair removed by shaving (i.e., hair mass) is reduced. Increase in hair growth is demonstrated when the opposite effect is observed.
Male intact Golden Syrian hamsters are considered acceptable models for human beard hair growth and other androgen-stimulated hair growth in that they display oval shaped flank organs, one on each side, each about 8 mm.ain major diameter, which grow thick black and coarse hair similar to human beard hair. These organs produce hair in response to androgens in the hamster. To evaluate tine effectiveness of a composition in reducing androgen-simulated hair growth, the flank organs of each of a group of hamsters are shaved. To one organ of each animal 10 ul.
of composition vehicle alone once a day is applied, while to the other organ of each animal an equal amount of the composition (including the relevant compound or compounds).
After thirteen applications (one application per day for five days a week), the flank organs are shaved and the amount of recovered hair (hair mass) from each is weighed.
Percent-reduction of hair growth is calculated by subtracting the hair mass (mg) value of the test compound treated side from the hair mass value of the vehicle treated side; the delta value obtained is then divided by the hair mass value of the vehicle treated side, and the resultant number is multiplied by 100.
The above-described assay will be referred to herein as the "Golden Syrian hamster" assay. Preferred compositions provide a reduction in hair growth of at least about 1S%, more preferably at least about 40%, and most to preferably at least about 60% when tested in the Golden Syrian hamster assay.
A number of compositions containing compounds that induce or activate UGTs for which testosterone is a substrate were tested in the Golden Syrian hamster assay; the results are provided in Table I:
TABLE I
Compound Vehicle Left (ma) Right (mg) ~ Inhibition ethoxyquin A 0.55 ~ .16 2.41 ~ .11 75 ~ 7 5,7-dihydroxy-4'-methoxyflavone B 1.00 ~ .22 2.61 ~ .27 62 ~ 9 butylhydroxy-anisole A 0.92 ~ .24 2.27 ~ .11 61 ~ 9 phenobarbital A 0.89 ~ .16 1.88 ~ .24 51 ~ 11 naringenin A 1.42 ~ .18 2.46 ~ .20 40 ~ 8 butylhydroxy-toluene C 1.74 ~ .38 2.05 ~ .36 22 ~ 18 flavanone C 1.91 ~ .22 2.39 ~ .22 17 ~ 10 All compounds were administered as a 10% dose. Vehicle A =
ethanol 80%, H20 17.5%, propylene glycol dipelargonate 2%, 3o propylene glycol 0.5%; B = ethanol 70%, dimethylsulfoxamine 30%; C = propylene glycol 50%, ethanol 25%, dimethylsulfoxide 25%.
_ 7 _ An assay was performed to evaluate whether some of the compounds tested in the Golden Syrian Hamster assay caused an induction of testosterone glucuronide formation.
Flank organ homogenates were prepared by adding 4 flank organs into 2 mL of a buffer containing 25 mM Tris/50 mM sucrose, pH 7.4 and homogenized with a PolytronT"" (Brinkman Instruments) while keeping the mixture on ice. The - 7a -glucuronidation of testosterone was measured by incubating the 20 ~cl of the flank organ protein (1 mg/ml) with (1'C) -testosterone 125uM and UDP-glucuronic acid (SmM) in the presence of buffer containing 0.5M Tris, pH 7.5 and 0.1 M
MgClz. The total reaction mixture volume was 100 /cl. Assay mixtures were incubated at 37°C for 60 minutes, and reactions were stopped with the addition of 3.5 ml methylene chloride. An aqueous carrier (250 ~,l water) was added to each reaction mixture which was then shaken and centrifuged.
The unmetabolized ("C)-testosterone remained in the organic.
phase whereas the testosterone glucuronide partitioned into the aqueous phase, and was quantitated by scintillation spectrometry. The results are provided in Table II:
TABLE II
Co'nd 96Indueyon e~hoxyquin Z14 bucylhydroxyaoisole 17a 3,7dihydroxy-4'~methoxyflavone pherobarbital l13 It was believed that the diversion of testostercale away from its biologically active species to a glucuronide or sulfonate conjugate would have effects on the flank organs of the Golden Syrian hamster since testosterone i~
known to regulate the existence of these unique organs. The diameter of flank organs were assessed using a caliper following topical treatment of the hamsters with ethoxyquin or 5,7-dihydroxy-4~-methoxyflavone as described in the hair mass assay section. A decrease in flank organ diameter was demonstrated following topical application of the compounds (Table III). These data are consistent with the hypothesis that suggests that local induction of conjugating enzymes, such as UGTs, can dimin=sh the biological activity of testosterone.
g _ TABLE III
~~°xy9~~ 7.18 * .IG a.a3 t .is l.GS * .37 l9 * 4 s.7dihydroxY-4'-me~hOXyflavotu 8.04 t .29 9.08 * .43 1.U4 * .16 12 t 5 Other embodiments are within the claims.
In another aspect, the invention features modulating hair growth by topical application of a compound that induces or activates the conversion of an androgen involved in hair growth to a less active (e. g., more water soluble) metabolite.
Other features and advantages of the invention will IO be apparent from the Description of Preferred Embodiments thereof, and from the claims.
Descrio~ion of Preferre Embodim rr,~
Compounds that activate or induce UGTs are known.
Such compounds include ethoxyquin, 5,7-dihydroxy-4'-methoxyflavone, butyihydroxyanisole, Phenobarbital, naringenin, butylhydroxytoluene, flavone, tioconazole, traps-1,2-bis(2-pyridyl)ethylene, 7,4'-isoflavandiol, (equol), galangin, 7-hydroxy-4'-methoxyisoflavone (formononetin), 5,4'-dihydroxy-7-methoxyisoflavone (prunetin), and daidzein. These compounds induce UGTs .~
relevant to testosterone glucononidation.
Examples of androgens that may be conjugated include testosterone, dihydrotestosterone, androstenedione, androstenediols, and dehydroepiandrosterone.
It is believed that the compounds act according to the pathway shown below (in which testosterone is used as an example):
swet~aon< -~. Ert~G~ow~soaW.aa,~
w~G~~c~) c«~uwiv. E~m., ~,~"~,k"",;~" ...... ~'~~t~ ~toaauter~se) T.~~.1 c.ue:.~) Denafed Bbl~nl Aauney --1 - 4 _ HawGwrthSomuVuos(~cilp) The compound may induce or activate, for example, UGTs that catalyze the conjugation of testosterone with glucuronic acid (donated from uridine diphosphoglucuronic acid) or STs that catalyze the conjugation of testosterone with a sulfonate group (donated from 3'-phosphoadenoaine S~-phosphosulfate).
The compound preferably is incorporated in a topical composition that includes a non-toxic dermatologically acceptable vehicle or carrier which is adapted to be spread l0 upon the skin. Examples of, suitable vehicles are acetone, alcohols, or a cream, lotion, or gel which can effectively deliver the active compound. A vehicle is disclosed in U.S.
Patent No. 5,648,394. In addition, a penetration enhancer may be added to the vehicle to further enhance the effectiveness of the formulation.
The concentration of the compound in the composition may be varied over a wide range up to a saturated solution, preferably from 0.1% to 30% by weight or even more; the reduction or increase in hair growth rises as the amount of inhibitor applied increases per unit area of skin. The-maximum amount effectively applied is limited only by the rate at which the compound penetrates the skin. The effective amounts may range, for example, from 10 to 3000 micrograms or more per square centimeter of skin.
A composition may include more than one of the compounds.
The composition should be topically applied to a selected area of the body from which it is desired to reduce hair growth (if the hair growth is androgen-stimulated hair growth) or increase hair growth (if the hair loss is androgen dependent). For example, in humans the composition can be applied to the face, particularly to the beard area of the face, i.e., the cheek, neck, upper lip, and chin to obtain a reduction in hair growth. .The composition can also be applied to the legs, arms, torso or armpits to obtain a reduction in hair growth. The composition can be applied to ~he scalp to obtain an increase in hair growth. The composition is particularly suitable for reducing the growth of unwanted hair in women suffering from hirsutism or other similar conditions.
in humans, the composition, for example, may be applied once or twice a day, or even more frequently, for two weeks to six months (e.g., three months) to achieve a perceived effect. Reduction in hair growth is demonstrated when the frequency of hair removal is reduced or the subject perceives less hair on the treated site, or quantitatively, when the weight of hair removed by shaving (i.e., hair mass) is reduced. Increase in hair growth is demonstrated when the opposite effect is observed.
Male intact Golden Syrian hamsters are considered acceptable models for human beard hair growth and other androgen-stimulated hair growth in that they display oval shaped flank organs, one on each side, each about 8 mm.ain major diameter, which grow thick black and coarse hair similar to human beard hair. These organs produce hair in response to androgens in the hamster. To evaluate tine effectiveness of a composition in reducing androgen-simulated hair growth, the flank organs of each of a group of hamsters are shaved. To one organ of each animal 10 ul.
of composition vehicle alone once a day is applied, while to the other organ of each animal an equal amount of the composition (including the relevant compound or compounds).
After thirteen applications (one application per day for five days a week), the flank organs are shaved and the amount of recovered hair (hair mass) from each is weighed.
Percent-reduction of hair growth is calculated by subtracting the hair mass (mg) value of the test compound treated side from the hair mass value of the vehicle treated side; the delta value obtained is then divided by the hair mass value of the vehicle treated side, and the resultant number is multiplied by 100.
The above-described assay will be referred to herein as the "Golden Syrian hamster" assay. Preferred compositions provide a reduction in hair growth of at least about 1S%, more preferably at least about 40%, and most to preferably at least about 60% when tested in the Golden Syrian hamster assay.
A number of compositions containing compounds that induce or activate UGTs for which testosterone is a substrate were tested in the Golden Syrian hamster assay; the results are provided in Table I:
TABLE I
Compound Vehicle Left (ma) Right (mg) ~ Inhibition ethoxyquin A 0.55 ~ .16 2.41 ~ .11 75 ~ 7 5,7-dihydroxy-4'-methoxyflavone B 1.00 ~ .22 2.61 ~ .27 62 ~ 9 butylhydroxy-anisole A 0.92 ~ .24 2.27 ~ .11 61 ~ 9 phenobarbital A 0.89 ~ .16 1.88 ~ .24 51 ~ 11 naringenin A 1.42 ~ .18 2.46 ~ .20 40 ~ 8 butylhydroxy-toluene C 1.74 ~ .38 2.05 ~ .36 22 ~ 18 flavanone C 1.91 ~ .22 2.39 ~ .22 17 ~ 10 All compounds were administered as a 10% dose. Vehicle A =
ethanol 80%, H20 17.5%, propylene glycol dipelargonate 2%, 3o propylene glycol 0.5%; B = ethanol 70%, dimethylsulfoxamine 30%; C = propylene glycol 50%, ethanol 25%, dimethylsulfoxide 25%.
_ 7 _ An assay was performed to evaluate whether some of the compounds tested in the Golden Syrian Hamster assay caused an induction of testosterone glucuronide formation.
Flank organ homogenates were prepared by adding 4 flank organs into 2 mL of a buffer containing 25 mM Tris/50 mM sucrose, pH 7.4 and homogenized with a PolytronT"" (Brinkman Instruments) while keeping the mixture on ice. The - 7a -glucuronidation of testosterone was measured by incubating the 20 ~cl of the flank organ protein (1 mg/ml) with (1'C) -testosterone 125uM and UDP-glucuronic acid (SmM) in the presence of buffer containing 0.5M Tris, pH 7.5 and 0.1 M
MgClz. The total reaction mixture volume was 100 /cl. Assay mixtures were incubated at 37°C for 60 minutes, and reactions were stopped with the addition of 3.5 ml methylene chloride. An aqueous carrier (250 ~,l water) was added to each reaction mixture which was then shaken and centrifuged.
The unmetabolized ("C)-testosterone remained in the organic.
phase whereas the testosterone glucuronide partitioned into the aqueous phase, and was quantitated by scintillation spectrometry. The results are provided in Table II:
TABLE II
Co'nd 96Indueyon e~hoxyquin Z14 bucylhydroxyaoisole 17a 3,7dihydroxy-4'~methoxyflavone pherobarbital l13 It was believed that the diversion of testostercale away from its biologically active species to a glucuronide or sulfonate conjugate would have effects on the flank organs of the Golden Syrian hamster since testosterone i~
known to regulate the existence of these unique organs. The diameter of flank organs were assessed using a caliper following topical treatment of the hamsters with ethoxyquin or 5,7-dihydroxy-4~-methoxyflavone as described in the hair mass assay section. A decrease in flank organ diameter was demonstrated following topical application of the compounds (Table III). These data are consistent with the hypothesis that suggests that local induction of conjugating enzymes, such as UGTs, can dimin=sh the biological activity of testosterone.
g _ TABLE III
~~°xy9~~ 7.18 * .IG a.a3 t .is l.GS * .37 l9 * 4 s.7dihydroxY-4'-me~hOXyflavotu 8.04 t .29 9.08 * .43 1.U4 * .16 12 t 5 Other embodiments are within the claims.
Claims (62)
PROPERTY OR PRIVILEGE IS CLAIMED ARE DEFINED AS FOLLOWS:
1. A method of reducing mammalian androgen-stimulated hair growth, which comprises:
selecting an area of skin from which hair grows in response to androgen-stimulation from which reduced hair growth is desired; and applying to said area of skin a dermatologically acceptable composition comprising a compound other than a 5-lipoxygenase inhibitor that induces or activates a UDP-glucuronosyltransferase or a sulfotransferase, wherein the compound is present in the composition in an amount effective to reduce hair growth.
selecting an area of skin from which hair grows in response to androgen-stimulation from which reduced hair growth is desired; and applying to said area of skin a dermatologically acceptable composition comprising a compound other than a 5-lipoxygenase inhibitor that induces or activates a UDP-glucuronosyltransferase or a sulfotransferase, wherein the compound is present in the composition in an amount effective to reduce hair growth.
2. A method of claim 1, wherein said compound comprises ethoxyquin.
3. The method of claim 1, wherein said compound comprises 5,7-dihydroxy-4'-methoxyflavone.
4. The method of claim 1, wherein said compound comprises butylhydroxyanisole.
5. The method of claim 1, wherein said compound comprises phenobarbital.
6. The method of claim 1, wherein said compound comprises naringenin.
7. The method of claim 1, wherein said compound comprises butylhydroxytoluene.
8. The method of claim 1, wherein said compound comprises flavone.
9. The method of claim 1, wherein said compound comprises tioconazole.
10. The method of claim 1, wherein said compound comprises trans-1,2-bis(2-pyridyl)ethylene.
11. The method of claim 1, wherein said compound comprises 7,4'-isoflavandiol.
12. The method of claim 1, wherein said compound comprises 7-hydroxy-4'-methoxyisoflavone.
13. The method of claim 1, wherein said compound comprises 5,4'-dihydroxy-7-methoxyisoflavone.
14. The method of claim 1, wherein said compound comprises daidzein.
15. The method of any one of claims 1 to 14, wherein said compound induces or activates a UDP-glucuronosyl-transferase.
16. The method of any one of claims 1 to 15, wherein said androgen comprises testosterone.
17. The method of any one of claims 1 to 16, wherein the concentration of said compound in said composition is between 0.1% and 30% by weight.
18. The method of any one of claims 1 to 17, wherein the composition provides a reduction in hair growth of at least 15% when tested in the Golden Syrian hamster assay.
19. The method of any one of claims 1 to 18, wherein the composition provides a reduction in hair growth of at least 40% when tested in the Golden Syrian hamster assay.
20. The method of any one of claims 1 to 19, wherein said mammal is a human.
21. The method of any one of claims 1 to 20, wherein the area of skin is on the face of the human.
22. The method of claim 21, wherein said human is a woman suffering from hirsutism.
23. A method of reducing mammalian androgen-stimulated hair growth, which comprises:
selecting an area of skin from which hair grows in response to androgen-stimulation from which reduced hair growth is desired; and applying to said area of skin a dermatologically acceptable composition comprising a compound that induces or activates the conjugation of an androgen that stimulates androgen-stimulated hair growth to produce a conjugate of the androgen, wherein the compound is present in the composition in an amount effective to reduce the hair growth.
selecting an area of skin from which hair grows in response to androgen-stimulation from which reduced hair growth is desired; and applying to said area of skin a dermatologically acceptable composition comprising a compound that induces or activates the conjugation of an androgen that stimulates androgen-stimulated hair growth to produce a conjugate of the androgen, wherein the compound is present in the composition in an amount effective to reduce the hair growth.
24. The method of claim 23, wherein the area of skin is on the face of a human.
25. The method of claim 23 or 24, wherein the compound is an inducer or activator of an androgen conjugation enzyme.
26. The method of claim 25, wherein the androgen comprises a testosterone.
27. The method of claim 25, wherein the androgen comprises dihydrotestosterone.
28. The method of claim 25, wherein the androgen comprises an androgen selected from the group consisting of androstenedione, androstenediols, and dehydroepiandrosterone.
29. A method of reducing mammalian androgen-stimulated hair growth, which comprises:
selecting an area of skin from which hair grows in response to androgen-stimulation from which reduced hair growth is desired; and applying to said area of skin a dermatologically acceptable composition comprising a compound other than a 5-lipoxygenase inhibitor that induces or activates the conversion of testosterone to a less active metabolite, wherein the compound is present in the composition in an amount effective to reduce the hair growth from the area of skin.
selecting an area of skin from which hair grows in response to androgen-stimulation from which reduced hair growth is desired; and applying to said area of skin a dermatologically acceptable composition comprising a compound other than a 5-lipoxygenase inhibitor that induces or activates the conversion of testosterone to a less active metabolite, wherein the compound is present in the composition in an amount effective to reduce the hair growth from the area of skin.
30. The method of claim 29, wherein the area of skin is on the face of a human.
31. The method of claim 29, wherein the less active metabolite comprises a compound that is more water soluble than testosterone.
32. Use of a compound other than a 5-lipoxygenase inhibitor that induces or activates a UDP-glucuronosyl-transferase or a sulfotransferase, for the manufacture of a dermatologically acceptable composition for reducing mammalian androgen-stimulated hair growth.
33. The use of claim 32, wherein said compound comprises ethoxyquin.
34. The use of claim 32, wherein said compound comprises 5,7-dihydroxy-4'-methoxyflavone.
35. The use of claim 32, wherein said compound comprises butylhydroxy-anisole.
36. The use of claim 32, wherein said compound comprises phenobarbital.
37. The use of claim 32, wherein said compound comprises naringenin.
38. The use of claim 32, wherein said compound comprises butylhydroxytoluene.
39. The use of claim 32, wherein said compound comprises flavone.
40. The use of claim 32, wherein said compound comprises tioconazole.
41. The use of claim 32, wherein said compound comprises trans-1,2-bis(2-pyridyl)ethylene.
42. The use of claim 32, wherein said compound comprises 7,4'-isoflavandiol.
43. The use of claim 32, wherein said compound comprises 7-hydroxy-4'-methoxyisoflavone.
44. The use of claim 32, wherein said compound comprises 5,4'-dihydroxy-7-methoxyisoflavone.
45. The use of claim 32, wherein said compound comprises diadzein.
46. The use of any one of claims 32 to 45, wherein said compound induces or activates a UDP-glucuronosyltransferase.
47. The use of any one of claims 32 to 46, wherein said androgen comprises testosterone.
48. The use of any one of claims 32 to 47, wherein the concentration of said compound in said composition is between 0.1% and 30% by weight.
49. The use of any one of claims 32 to 48, wherein the composition provides a reduction in hair growth of at least 15% when tested in the Golden Syrian hamster assay.
50. The use of any one of claims 32 to 49, wherein the composition provides a reduction in hair growth of at least 40% when tested in the Golden Syrian hamster assay.
51. The use of any one of claims 32 to 50, wherein said mammal is a human.
52. The use of any one of claims 32 to 51, wherein the area of skin is on the face of a human.
53. The use of claim 52, wherein said human is a woman suffering from hirsutism.
54. Use of a compound that induces or activates the conjugation of an androgen that stimulates androgen-stimulated hair growth to produce a conjugate of the androgen for the manufacture of a dermatologically acceptable composition for reducing mammalian androgen-stimulated hair growth.
55. The use of claim 54, wherein the area of skin is on the face of a human.
56. The use of claim 54 or 55, wherein the compound is an inducer or activator of an androgen conjugation enzyme.
57. The use of claim 56, wherein the androgen comprises a testosterone.
58. The use of claim 56, wherein the androgen comprises dihydro-testosterone.
59. The use of claim 56, wherein the androgen comprises an androgen selected from the group consisting of androstenedione, androstenediols, and dehydro-epiandrosterone.
60. The use of a compound other than a 5-lipoxygenase inhibitor that induces or activates the conversion of testosterone to a less active metabolite, for the manufacture of a dermatologically acceptable composition for reducing mammalian androgen-stimulated hair growth.
61. The use of claim 60, wherein the area of skin is on the face of a human.
62. The use of claim 60, wherein the less active metabolite comprises a compound that is more water soluble than testosterone.
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US09/009,213 | 1998-01-20 | ||
US09/009,213 US5958946A (en) | 1998-01-20 | 1998-01-20 | Modulation of hair growth |
PCT/US1999/001093 WO1999036067A1 (en) | 1998-01-20 | 1999-01-19 | Modulation of hair growth |
Publications (2)
Publication Number | Publication Date |
---|---|
CA2320160A1 CA2320160A1 (en) | 1999-07-22 |
CA2320160C true CA2320160C (en) | 2004-11-02 |
Family
ID=21736267
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CA002320160A Expired - Fee Related CA2320160C (en) | 1998-01-20 | 1999-01-19 | Modulation of hair growth |
Country Status (10)
Country | Link |
---|---|
US (1) | US5958946A (en) |
EP (1) | EP1047420B2 (en) |
AR (1) | AR014438A1 (en) |
AT (1) | ATE359103T1 (en) |
AU (1) | AU758588B2 (en) |
BR (1) | BR9907090A (en) |
CA (1) | CA2320160C (en) |
DE (1) | DE69935778T3 (en) |
ES (1) | ES2281167T5 (en) |
WO (1) | WO1999036067A1 (en) |
Families Citing this family (40)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP3973748B2 (en) | 1998-01-14 | 2007-09-12 | 花王株式会社 | Hair growth inhibitor |
US7985404B1 (en) * | 1999-07-27 | 2011-07-26 | Johnson & Johnson Consumer Companies, Inc. | Reducing hair growth, hair follicle and hair shaft size and hair pigmentation |
US6235737B1 (en) | 2000-01-25 | 2001-05-22 | Peter Styczynski | Reduction of hair growth |
FR2807323A1 (en) | 2000-04-10 | 2001-10-12 | Oreal | COMPOSITION, ESPECIALLY COSMETIC, CONTAINING A STEROID AND A 2-ALKYL ALKANOL OR AN ESTER |
US6299865B1 (en) | 2000-05-02 | 2001-10-09 | Peter Styczynski | Reduction of hair growth |
US7439271B2 (en) | 2001-06-27 | 2008-10-21 | The Gillette Company | Reduction of hair growth |
JP4759182B2 (en) * | 2001-08-03 | 2011-08-31 | 花王株式会社 | Water-soluble ginger extract |
US6743822B2 (en) | 2001-08-10 | 2004-06-01 | The Gillette Company | Reduction of hair growth |
US7261878B2 (en) * | 2001-08-10 | 2007-08-28 | The Gillette Company | Reduction of hair growth |
US20030036561A1 (en) * | 2001-08-10 | 2003-02-20 | Peter Styczynski | Reduction of hair growth |
US7160921B2 (en) * | 2002-01-29 | 2007-01-09 | The Gillette Company | Reduction of hair growth |
US20040198821A1 (en) * | 2002-01-29 | 2004-10-07 | Hwang Cheng Shine | Reduction of hair growth |
US20030199584A1 (en) * | 2002-04-11 | 2003-10-23 | Ahluwalia Gurpreet S. | Reduction of hair growth |
CA2492754C (en) * | 2002-07-24 | 2018-05-22 | Children's Hospital Medical Center | Compositions and products containing enantiomeric equol, and methods for their making |
US8668914B2 (en) * | 2002-07-24 | 2014-03-11 | Brigham Young University | Use of equol for treating skin diseases |
US8580846B2 (en) | 2002-10-29 | 2013-11-12 | Brigham Young University | Use of equol for ameliorating or preventing neuropsychiatric and neurodegenerative diseases or disorders |
AU2005239984B2 (en) * | 2002-10-29 | 2010-06-03 | Brigham Young University | Use of equol for treating skin diseases |
EP1569636B1 (en) | 2002-10-29 | 2017-12-13 | Colorado State University Research Foundation | Use of equol for treating androgen mediated diseases |
US20040141935A1 (en) * | 2003-01-21 | 2004-07-22 | Peter Styczynski | Reduction of hair growth |
US20050003024A1 (en) * | 2003-03-04 | 2005-01-06 | The Procter & Gamble Company | Regulation of mammalian hair growth |
US7015349B2 (en) * | 2003-03-26 | 2006-03-21 | The Gillette Company | Reduction of hair growth |
US20050112075A1 (en) * | 2003-11-25 | 2005-05-26 | Hwang Cheng S. | Reduction of hair growth |
ZA200605378B (en) * | 2003-12-22 | 2008-01-30 | Alcon Inc | Agents for treatment of diabetic retinopathy and drusen formation in macular degeneration |
US20050249685A1 (en) * | 2004-04-27 | 2005-11-10 | Natalia Botchkareva | Reduction of hair growth |
KR20070086431A (en) * | 2004-12-22 | 2007-08-27 | 더 지렛트 캄파니 | Reduction of hair growth with survivin inhibitors |
MX2007007623A (en) * | 2004-12-22 | 2007-08-03 | Gillette Co | Reduction of hair growth. |
WO2006084312A1 (en) * | 2005-02-09 | 2006-08-17 | Acrux Dds Pty Ltd | Method of promoting hair growth |
US7618956B2 (en) * | 2005-05-31 | 2009-11-17 | The Gillette Company | Reduction of hair growth |
US20070059264A1 (en) * | 2005-09-13 | 2007-03-15 | Ahluwalia Gurpreet S | Reduction of hair growth |
KR100817662B1 (en) | 2006-03-23 | 2008-03-27 | 주식회사 엘지생활건강 | c-Kit activation inhibitor, skin whitening compound and composition for skin whitening containing the same |
US7727516B2 (en) * | 2006-02-28 | 2010-06-01 | The Procter & Gamble Company | Reduction of hair growth |
FR2902326B1 (en) | 2006-06-20 | 2008-12-05 | Oreal | USE OF COUMARIN, BUTYLATED HYDROXYANISOLE AND ETHOXYQUINE FOR THE TREATMENT OF CANITIA |
US20080059313A1 (en) * | 2006-08-30 | 2008-03-06 | Oblong John E | Hair care compositions, methods, and articles of commerce that can increase the appearance of thicker and fuller hair |
FR2908652B1 (en) * | 2007-01-22 | 2012-09-28 | Oreal | USE OF ETHOXUQUINE FOR THE TREATMENT OF CANITIA |
FR2902320B1 (en) * | 2007-01-22 | 2008-12-05 | Oreal | USE OF BUTYLATED HYDROXYANISOLE FOR THE TREATMENT OF CANITIA |
US8691518B2 (en) * | 2010-09-24 | 2014-04-08 | Global Life Science Partners Limited | Systems and methods for predicting response to minoxidil for the treatment of androgenetic alopecia |
US9588118B2 (en) | 2010-09-24 | 2017-03-07 | Follea International | Devices for performing colorimetric assay with plucked human hair |
US10633688B2 (en) | 2010-09-24 | 2020-04-28 | Follea International | Systems and methods for predicting response to minoxidil for the treatment of androgenetic alopecia |
KR101664531B1 (en) * | 2013-02-14 | 2016-10-11 | 경희대학교 산학협력단 | Composition for prevention of depilation and improvement of hair growth comprising Formononetin |
WO2017085687A1 (en) | 2015-11-20 | 2017-05-26 | West-Ward Pharmaceuticals International Limited | Stable formulation of phenobarbital sodium injection |
Family Cites Families (48)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3426137A (en) * | 1965-12-23 | 1969-02-04 | Olin Mathieson | Hair growth inhibiting by aminobenzophenones |
US4161540A (en) * | 1966-08-22 | 1979-07-17 | Schering Corporation | Antiandrogenic agents and methods for the treatment of androgen dependent disease states |
GB1458349A (en) * | 1972-12-05 | 1976-12-15 | Sykora F | Composition for and a process therewith of treating the hair and/or scalps of animals |
US4039669A (en) * | 1975-08-01 | 1977-08-02 | Sterling Drug Inc. | Composition for topical application and use thereof |
US4139638A (en) * | 1976-09-23 | 1979-02-13 | Schering Corporation | Methods for the treatment of hirsutism |
FR2380775A1 (en) * | 1977-02-22 | 1978-09-15 | Sederma Sarl | "AFTER-DEPILATION" COMPOSITION PROMOTING A PROGRESSIVE SLOWING OF HAIR REGROWTH |
US4191775A (en) * | 1977-12-15 | 1980-03-04 | Imperial Chemical Industries Limited | Amide derivatives |
US4269831A (en) * | 1979-05-09 | 1981-05-26 | Sterling Drug Inc. | Topical dermatological method of use of an androstenopyrazole |
US4439432A (en) * | 1982-03-22 | 1984-03-27 | Peat Raymond F | Treatment of progesterone deficiency and related conditions with a stable composition of progesterone and tocopherols |
JP2519024B2 (en) * | 1982-06-07 | 1996-07-31 | 花王株式会社 | Hair cosmetics |
US4508714A (en) * | 1983-11-14 | 1985-04-02 | Tihomir Cecic | Organic scalp lotion |
US4885289A (en) * | 1983-12-12 | 1989-12-05 | Breuer Miklos M | Alteration of character of male beard growth |
EP0173181A1 (en) † | 1984-08-16 | 1986-03-05 | Akio Fujikawa | Anti oxidation composition |
US4720489A (en) * | 1984-10-15 | 1988-01-19 | Douglas Shander | Hair growth modification with ornithine decarboxylase inhibitors |
US4935231A (en) * | 1985-08-28 | 1990-06-19 | Repligen Corporation | Use of thioredoxin, thioredoxin-derived, or thioredoxin-like dithiol peptides in hair care preparations |
FR2588186B1 (en) † | 1985-10-09 | 1987-12-18 | Thorel Jean | COMPOSITION FOR DELAYING HAIR GROWTH |
US5091171B2 (en) * | 1986-12-23 | 1997-07-15 | Tristrata Inc | Amphoteric compositions and polymeric forms of alpha hydroxyacids and their therapeutic use |
LU86944A1 (en) † | 1987-07-17 | 1989-03-08 | Oreal | COMPOSITION BASED ON HYDROXYPYRIDONE DERIVATIVES FOR REDUCING HAIR LOSS |
GB8720937D0 (en) † | 1987-09-05 | 1987-10-14 | Boots Co Plc | Depilatory compositions |
JPH085788B2 (en) * | 1987-10-08 | 1996-01-24 | 花王株式会社 | 5α-reductase inhibitor |
US5096911A (en) * | 1990-06-25 | 1992-03-17 | Ahluwalia Gurpreet S | Alteration of rate and character of hair growth |
EP0543949B1 (en) * | 1990-08-14 | 1997-10-22 | HANDELMAN, Joseph H. | Enzymic alteration of hair growth |
US5189212A (en) * | 1990-09-07 | 1993-02-23 | University Of Georgia Research Foundation, Inc. | Triarylethylene carboxylic acids with estrogenic activity |
US5095007A (en) * | 1990-10-24 | 1992-03-10 | Ahluwalia Gurpreet S | Alteration of rate and character of hair growth |
DE4038693A1 (en) * | 1990-12-05 | 1992-06-11 | Heverhagen Ulrich | MEANS TO REDUCE GROWTH OR TO REMOVE HAIR ON HUMAN BODY |
US5143925A (en) * | 1990-12-20 | 1992-09-01 | Douglas Shander | Alteration of rate and character of hair growth |
GB9118866D0 (en) * | 1991-09-04 | 1991-10-23 | Unilever Plc | Cosmetic composition |
GB9118979D0 (en) * | 1991-09-04 | 1991-10-23 | Unilever Plc | Cosmetic composition |
US5364885A (en) * | 1992-11-13 | 1994-11-15 | Ahluwalia Gurpreet S | Reduction of hair growth |
US5411991A (en) * | 1992-12-22 | 1995-05-02 | Shander; Douglas | Method of reducing hair growth employing sulfhydryl active compounds |
DE69434149T2 (en) * | 1993-03-09 | 2006-07-20 | University Of Utah Research Foundation, Salt Lake City | USE OF DHEA OR ITS DERIVATIVES FOR THE MANUFACTURE OF A MEDICAMENT FOR PREVENTING PROGRESSIVE TISSUE NEKROSIS, REPERFUSION INJURY, BACTERIAL TRANSLATION, AND ATOMIC SYNDROME IN ADULTS |
US5648394A (en) * | 1993-05-27 | 1997-07-15 | Boxall; Brian Alfred | Topical composition for inhibiting hair growth |
JPH072677A (en) † | 1993-06-18 | 1995-01-06 | Toyo Seito Kk | Peroral hair-growing agent |
JP3597210B2 (en) * | 1993-08-27 | 2004-12-02 | 花王株式会社 | Hair restoration |
FR2711060B1 (en) * | 1993-10-13 | 1995-11-17 | Oreal | Method for modifying the growth of hair and / or hair and compositions which can be used for this purpose. |
US5474763A (en) * | 1994-03-11 | 1995-12-12 | Shander; Douglas | Reduction of hair growth |
US5455234A (en) * | 1994-03-16 | 1995-10-03 | Ahluwalia; Gurpreet S. | Inhibition of hair growth |
DE4432947C2 (en) † | 1994-09-16 | 1998-04-09 | New Standard Gmbh | Agent for the treatment of the skin and its use |
US5554608A (en) * | 1994-09-28 | 1996-09-10 | Ahluwalia; Gurpreet S. | Inhibition of hair growth |
GB9419715D0 (en) * | 1994-09-30 | 1994-11-16 | Boots Co Plc | Hair stimulant composition |
EP0812185B1 (en) * | 1995-02-28 | 2002-07-03 | The Gillette Company | Use of angiogenesis suppressors for inhibiting hair growth |
US5639785A (en) * | 1995-06-07 | 1997-06-17 | Global Pharma, Ltd. | Methods for the treatment of baldness and gray hair using isoflavonoid derivatives |
AU5970496A (en) * | 1995-06-07 | 1996-12-30 | Patrick C. Kung | Compounds and methods for promoting hair growth |
US5773005A (en) * | 1995-06-09 | 1998-06-30 | Takahashi; Hidehiko | Purified flavonoid and diterpene 5α-reductase inhibitors from thuja orientalis for androgen-related diseases |
FR2747568B1 (en) * | 1996-04-17 | 1999-09-17 | Oreal | USE OF AT LEAST ONE LIPOXYGENASE INHIBITOR AND AT LEAST ONE CYCLO-OXYGENASE INHIBITOR FOR MODIFYING HAIR AND / OR HAIR GROWTH |
AUPO203996A0 (en) * | 1996-08-30 | 1996-09-26 | Novogen Research Pty Ltd | Therapeutic uses |
AU7165798A (en) * | 1997-04-28 | 1998-11-24 | Anticancer, Inc. | Use of genistein and related compounds to treat certain sex hormone related conditions |
EP1027045A4 (en) * | 1997-10-31 | 2004-12-08 | Arch Dev Corp | Methods and compositions for regulation of 5-alpha reductase activity |
-
1998
- 1998-01-20 US US09/009,213 patent/US5958946A/en not_active Expired - Lifetime
-
1999
- 1999-01-19 ES ES99903183T patent/ES2281167T5/en not_active Expired - Lifetime
- 1999-01-19 EP EP99903183A patent/EP1047420B2/en not_active Expired - Lifetime
- 1999-01-19 BR BR9907090-1A patent/BR9907090A/en not_active Application Discontinuation
- 1999-01-19 WO PCT/US1999/001093 patent/WO1999036067A1/en active IP Right Grant
- 1999-01-19 CA CA002320160A patent/CA2320160C/en not_active Expired - Fee Related
- 1999-01-19 AT AT99903183T patent/ATE359103T1/en not_active IP Right Cessation
- 1999-01-19 DE DE69935778T patent/DE69935778T3/en not_active Expired - Lifetime
- 1999-01-19 AU AU23266/99A patent/AU758588B2/en not_active Ceased
- 1999-01-20 AR ARP990100212A patent/AR014438A1/en unknown
Also Published As
Publication number | Publication date |
---|---|
DE69935778T3 (en) | 2012-01-19 |
AR014438A1 (en) | 2001-02-28 |
DE69935778D1 (en) | 2007-05-24 |
US5958946A (en) | 1999-09-28 |
ES2281167T3 (en) | 2007-09-16 |
AU2326699A (en) | 1999-08-02 |
AU758588B2 (en) | 2003-03-27 |
DE69935778T2 (en) | 2007-12-27 |
ES2281167T5 (en) | 2011-11-16 |
EP1047420B2 (en) | 2011-08-24 |
CA2320160A1 (en) | 1999-07-22 |
EP1047420A1 (en) | 2000-11-02 |
WO1999036067A1 (en) | 1999-07-22 |
EP1047420A4 (en) | 2004-04-14 |
ATE359103T1 (en) | 2007-05-15 |
BR9907090A (en) | 2001-09-04 |
EP1047420B1 (en) | 2007-04-11 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CA2320160C (en) | Modulation of hair growth | |
US6060471A (en) | Reduction of hair growth | |
US5455234A (en) | Inhibition of hair growth | |
US5474763A (en) | Reduction of hair growth | |
US5468476A (en) | Reduction of hair growth | |
US5728736A (en) | Reduction of hair growth | |
EP1033962B1 (en) | Reduction of hair growth | |
MXPA97002272A (en) | Inhibition of cabe growth | |
EP0957891B1 (en) | Reduction of hair growth | |
US7439271B2 (en) | Reduction of hair growth | |
MXPA00007074A (en) | Modulation of hair growth | |
MXPA00007125A (en) | Reduction of hair growth |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
EEER | Examination request | ||
MKLA | Lapsed |
Effective date: 20150119 |